Donohue T M, Chaisson M L, Zetterman R K
Liver Study Unit, VA Medical Center, Omaha, Nebraska 68105.
Alcohol Clin Exp Res. 1991 Feb;15(1):7-12. doi: 10.1111/j.1530-0277.1991.tb00512.x.
The present study was conducted to determine whether the antisecretory agents colchicine and ethanol affect the intracellular degradation of plasma proteins in rat liver. Plasma proteins were prelabeled in vivo with [3H]leucine and their levels were monitored immunochemically in both the medium and extracts of rat liver slices incubated alone or in the presence of 50 microM colchicine or 25 mM ethanol. Compared with those left untreated, colchicine-treated slices had a 40-55% lower secretory capacity and, at one point, showed significant hepatocellular retention of total plasma proteins. Plasma protein secretion by ethanol-treated liver slices was 22-32% lower than controls, but there was no detectable retention of unsecreted plasma proteins in the ethanol-treated liver tissue. In all experiments, the total radioactivity in plasma proteins (i.e., the immunoprecipitable radioactivity in the liver plus that in the medium) decreased with time in a manner suggestive of intracellular degradation. Regression analyses of the rates of degradation of presecretory proteins revealed that compared with controls, plasma protein catabolism was accelerated 57% in colchicine-treated slices. In ethanol-treated liver slices, there was a 50% increase in the degradation of total plasma proteins and a 46% increase in albumin catabolism. In all cases, degradation was intracellular. These findings indicate that inhibition of hepatic protein secretion by either colchicine or ethanol is associated with accelerated catabolism of unsecreted plasma proteins, suggesting that hepatocellular degradative processes are responsive to changes in the levels of presecretory proteins and/or perturbations of the secretory process.
本研究旨在确定抗分泌剂秋水仙碱和乙醇是否会影响大鼠肝脏中血浆蛋白的细胞内降解。血浆蛋白在体内用[³H]亮氨酸进行预标记，然后在单独孵育或存在50微摩尔秋水仙碱或25毫摩尔乙醇的情况下，对大鼠肝切片的培养基和提取物中的血浆蛋白水平进行免疫化学监测。与未处理的切片相比，用秋水仙碱处理的切片分泌能力降低了40 - 55%，并且在某一时刻，显示出总血浆蛋白在肝细胞中的显著滞留。用乙醇处理的肝切片的血浆蛋白分泌比对照组低22 - 32%，但在乙醇处理的肝组织中未检测到未分泌血浆蛋白的滞留。在所有实验中，血浆蛋白中的总放射性（即肝脏中可免疫沉淀的放射性加上培养基中的放射性）随时间下降，提示细胞内降解。对分泌前蛋白降解速率的回归分析表明，与对照组相比，用秋水仙碱处理的切片中血浆蛋白分解代谢加速了57%。在乙醇处理的肝切片中，总血浆蛋白降解增加了50%，白蛋白分解代谢增加了46%。在所有情况下，降解均发生在细胞内。这些发现表明，秋水仙碱或乙醇对肝脏蛋白分泌的抑制与未分泌血浆蛋白分解代谢的加速有关，这表明肝细胞降解过程对分泌前蛋白水平的变化和/或分泌过程的扰动有反应。
